Repercussions of hypo and hyperthyroidism on the heart circadian clock

Author(s)

Peliciari-Garcia, Rodrigo A. ^{[1, 2]} ; Bargi-Souza, Paula ^[1] ; Young, Martin E. ^[3] ; Nunes, Maria Tereza ^[1]

Affiliation

^[1] Univ Sao Paulo, Inst Biomed Sci 1, Dept Physiol & Biophys, Sao Paulo - Brazil

^[2] Univ Fed Sao Paulo, Dept Biol Sci, Morphophysiol & Pathol Sect, Diadema - Brazil

^[3] Univ Alabama Birmingham, Dept Med, Div Cardiovasc Dis, Birmingham, AL 35294 - USA

• Document type: Journal article
• Source: CHRONOBIOLOGY INTERNATIONAL; v. 35, n. 2, p. 147-159, 2018.
• Web of Science Citations: 6

Abstract

Myocardial gene expression and metabolism fluctuate over the course of the day in association with changes in energy supply and demand. Time-of-day-dependent oscillations in myocardial processes have been linked to the intrinsic cardiomyocyte circadian clock. Triiodothyronine (T3) is an important modulator of heart metabolism and function. Recently, our group has reported time-of-day-dependent rhythms in cardiac T3 sensitivity, as well as, T3-mediated acute alterations on core clock components. Hypo and hyperthyroidism are the second most prevalent endocrine disease worldwide. Considering the importance of the cardiomyocyte circadian clock and T3 to cardiac physiology, the aim of this study was to investigate the consequences of chronic hypo and hyperthyroidism on 24-h rhythms of circadian clock genes in the heart. Hypo and hyperthyroidism was induced in rats by thyroidectomy (Tx) and i.p. injections of supraphysiological dose of T3, respectively. Here we report alterations in mRNA levels of the major core clock components (Bmal1, Per2, Nr1d1, and Rora) for both experimental conditions (with the exception of Per2 during hyperthyroid condition). Oscillations in mRNA levels of key glucose and fatty-acid metabolism genes known to be clock controlled (Pdk4, Ucp3, Acot1, and Cd36) were equally affected by the experimental conditions, especially during the hypothyroid state. These findings suggest that chronic alterations in thyroid status significantly impacts 24-h rhythms in circadian clock and metabolic genes in the heart. Whether these perturbations contribute toward the pathogenesis of cardiac dysfunction associated with hypo and hyperthyroidism requires further elucidation. (AU)

• FAPESP's process: 13/05629-4 - Genomic vs nongenomic actions of thyroid hormones: changes of paradigms, physiological implications and therapeutical perspectives
• Grantee: Maria Tereza Nunes
• Support Opportunities: Research Projects - Thematic Grants
• FAPESP's process: 14/25888-7 - Characterization of the molecular basis involved on the expression of circadian clock genes in the pituitary at different thyroid states and the consequences for the synthesis/secretion of anterior pituitary hormones
• Grantee: Paula Bargi de Souza
• Support Opportunities: Scholarships in Brazil - Post-Doctoral